In PNx rats, we studied effects of 3E9 anti-MBG monoclonal antibody (mAb) on BP and cardiac hypertrophy and fibrosis. In PNx rats, a four-fold elevation in plasma MBG levels was associated with hypertension, increased cardiac levels of carbonylated protein, cardiac hypertrophy, a reduction in cardiac expression of a nuclear transcription factor which is a negative regulator of collagen synthesis, Fli-1, and an increase in the levels of collagen-1. A single intraperitoneal administration of 3E9 mAb to PNx rats reduced BP by 59 mmHg for 7 days and significantly reduced cardiac weight and cardiac levels of oxidative stress. These effects were associated with an increase in the expression of Fli-1, and a reduction in cardiac fibrosis. Thus, in chronic renal failure MBG contributes to hypertension and induces cardiac fibrosis via suppression of Fli-1, representing a potential target for therapy. Because previously in uremic rats active immunization against MBG reduced cardiac fibrosis but minimally affected BP, we hypothesized that MBG induces vascular fibrosis via BP-independent mechanism. We determined BP, plasma and urinary MBG, aortic collagen-1, and vascular function in NaCl-loaded male Wistar rats with streptozotocin-induced type 2 diabetes mellitus (DM-NaCl) and in control animals. Isolated rings of thoracic aortae were tested for their responsiveness to sodium nitroprusside (SNP) following endothelin-1-induced constriction. DM-NaCl rats exhibited a 3.5-fold increase in MBG excretion and 2.5-fold increase in levels of collagen-1 in thoracic aortae without changes of BP. As compared to control, aortic rings from DM-NaCl rats exhibited impaired response to the relaxant effect of SNP. In vivo administration of 3E9 mAb to DM-NaCl rats did not affect BP, but reduced aortic levels of collagen-1, and restored sensitivity of aortic rings to SNP. Thus, MBG is capable to increase vascular stiffness without affecting BP.